Studies on the toxicity of chemicals to humans are limited by the inaccessibility of most tissues, with the exception of certain biopsies and post-mortem samples. In order to monitor chemical exposure and to predict health effects in workers and the general population, it is necessary to develop, through animal experimentation, indicators of biochemical and cellular toxicity applicable to human studies. Among the thousands of chemicals used in the industrial and agricultural setting, many are known to affect the central and/or peripheral nervous system. Yet, very few peripheral indicators, accessible in humans, of nervous system toxicity are available. This proposal will focus on the muscarinic receptor, a component of the cholinergic system, which plays an important role in CNS functions as well as in the control of most of the body's organs. The hypothesis that will be tested is that muscarinic receptors on circulating lymphocytes could represent a marker of the same receptors in the CNS, the lung and other solid tissues and that alterations of muscarinic receptors in such tissues due to environmental or genetic factors, to pharmacological treatment or to chemical exposure, will be detected by measuring receptor density, affinity and function in lymphocytes. The specific aims that this project will address are: (1) To extensively characterize muscarinic cholinergic receptors on circulating lymphocytes of rats; (2) To establish a correlation between alterations of muscarinic receptors in solid tissues, induced by treatments with cholinergic agonists and antagonists and by chronic exposure to organophosphates, and alteration of muscarinic receptors in lymphocytes. These studies will provide important data on the biochemical and functional characteristics of muscarinic receptors on lymphocytes and on the possibility of the use of these receptors as markers of muscarinic receptors in tissues not accessible in humans. This knowledge will be useful for further studies involving the assessment of the effect of exposure of humans to chemicals affecting the nervous system.